Nonperturbative shell-model interactions from the in-medium similarity renormalization group.

We present the first ab initio construction of valence-space Hamiltonians for medium-mass nuclei based on chiral two- and three-nucleon interactions using the in-medium similarity renormalization group. When applied to the oxygen isotopes, we find experimental ground-state energies are well reproduced, including the flat trend beyond the drip line at (24)O. Similarly, natural-parity spectra in (21,22,23,24)O are in agreement with experiment, and we present predictions for excited states in (25,26)O. The results exhibit a weak dependence on the harmonic-oscillator basis parameter and reproduce spectroscopy within the standard sd valence space.

Electronic screening-enhanced hole pairing in two-leg spin ladders studied by high-resolution resonant inelastic x-ray scattering at Cu M edges.

We study the electronic screening mechanisms of the effective Coulomb on-site repulsion in hole-doped Sr(14)Cu(24)O(41) compared to undoped La(6)Ca(8)Cu(24)O(41) using polarization dependent high-resolution resonant inelastic x-ray scattering at Cu M edges. By measuring the energy of the effective Coulomb on-site repulsion and the spin excitations, we estimate superexchange and hopping matrix element energies along rungs and legs, respectively. Interestingly, hole doping locally screens the Coulomb on-site repulsion reducing it by as much as 25%. We suggest that the increased ratio of the electronic kinetic to the electronic correlation energy contributes to the local superexchange mediated pairing between holes.

Ab Initio calculations of even oxygen isotopes with chiral two-plus-three-nucleon interactions.

We formulate the in-medium similarity renormalization group (IM-SRG) for open-shell nuclei using a multireference formalism based on a generalized Wick theorem introduced in quantum chemistry. The resulting multireference IM-SRG (MR-IM-SRG) is used to perform the first ab initio study of all even oxygen isotopes with chiral nucleon-nucleon and three-nucleon interactions, from the proton to the neutron drip lines. We obtain an excellent reproduction of experimental ground-state energies with quantified uncertainties, which is validated by results from the importance-truncated no-core shell model and the coupled cluster method. The agreement between conceptually different many-body approaches and experiment highlights the predictive power of current chiral two- and three-nucleon interactions, and establishes the MR-IM-SRG as a promising new tool for ab initio calculations of medium-mass nuclei far from shell closures.

Palliative and end-of-life care training during the surgical clerkship.

BACKGROUND: In 2000, the Liaison Committee on Medical Education required that all medical schools provide experiential training in end-of-life care. To adhere to this mandate and advance the professional development of medical students, experiential training in communication skills at the end-of-life was introduced into the third-year surgical clerkship curriculum at Wright State University Boonshoft School of Medicine. MATERIALS AND METHODS: In the 2007-08 academic year, 97 third-year medical students completed six standardized end-of-life care patient scenarios commonly encountered during the third-year surgical clerkship. Goals and objectives were outlined for each scenario, and attending surgeons graded student performances and provided formative feedback. RESULTS: All 97 students, 57.7% female and average age 25.6 ± 2.04 y, had passing scores on the scenarios: (1) Adult Hospice, (2) Pediatric Hospice, (3) Do Not Resuscitate, (4) Dyspnea Management/Informed Consent, (5) Treatment Goals and Prognosis, and (6) Family Conference. Scenario scores did not differ by gender or age, but students completing the clerkship in the first half of the year scored higher on total score for the six scenarios (92.8% ± 4.8% versus 90.5% ± 5.0%, P = 0.024). CONCLUSIONS: Early training in end-of-life communication is feasible during the surgical clerkship in the third-year of medical school. Of all the scenarios, "Conducting a Family Conference" proved to be the most challenging.

A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells.

Necrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. Gp130 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti-gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in approximately 90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PR3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a different, structurally related 130-kD membrane protein on the cell surface of renal microvascular endothelial cells are autoantigenic targets for ANCA in patients with active NCGN.

Altered immune responses in interleukin 10 transgenic mice.

Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigen-specific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4(+) CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.

Emerging infectious diseases: public health issues for the 21st century.

Infectious diseases are the third leading cause of death in the United States and the leading cause worldwide. As the new millennium approaches, the public health community must replenish capacity depleted during years of inadequate funding while simultaneously incorporating new technologies and planning for the longer term. Among the challenges facing the public health community is the need for coordinated, global, multisectoral approaches to preventing and controlling complex infectious disease problems.

Modeling the effect of facial topographies upon the visual field of humans and primates.

PURPOSE: To establish a virtual device that can predict the effect of facial features on the visual field of humans and primates. METHODS: Virtual masks were obtained from human subjects, and macaque, chimpanzee and baboon taxidermic specimens, and aligned with upright head orientation at the center of a virtual perimeter-like dome (radius = 50 m) developed with Cinema 4D. Virtual searchlights positioned at the masks' pupils were then allowed to 'paint' facial elements obstructing their path, and demarcate the unobstructed rays at the perimetric surface and on a virtual ground floor related to eye level. Searchlight positions along the human mask's pupillary axis were identified by maximum congruence to Goldmann visual field limits. RESULTS: The human contours largely concur with large-stimulus isopters displaying the limiting role of the nasal ridge, and the relatively extended ventral and temporal limits. In contrast, the facial design of chimpanzees and baboons obstructs significant portions of the ventral foreground (>2 m cf < 0.5 m in human), while there appear to be larger binocular overlaps (125 degrees in chimp cf 90 degrees in human). CONCLUSIONS: The model provides information on anatomical constraints for monocular and binocular visual field extensions including projection of the ventral field on a virtual floor.

Effect of ClAlPcS(2) photodynamic and sonodynamic therapy on HeLa cells.

Photodynamic therapy (PDT) uses photosensitive substance to provoke a cytotoxic reaction causing a cell damage or cell death. The substances, photosensitizers, are usually derivates of porphyrine or phtalocyanine. Photosensitizers must be activated by light in order to produce reactive oxygen species, mainly singlet oxygen. Sonodynamic therapy (SDT) utilizes ultrasound to enhance a cytotoxic effects of compounds called sonosensitizers. In this study we investigated photodynamic and sonodynamic effect of chloraluminium phtalocyanine disulfonate (ClAlPcS(2)) on HeLa cells. DNA damage, cell viability and reactive oxygen species (ROS) production were assessed to find whether the combination of PDT and SDT inflicts HeLa cells more than PDT alone. We found that the combined therapy increases DNA fragmentation, enhances ROS production and decreases cell survival. Our results indicate that ClAlPcS(2) can act as a sonosentitiser and combined with PDT causes more irreversible changes to the cells resulting in cell death than PDT alone.

[Long-term results of scleral buckling using a microsurgical approach]. / Langzeitresultate nach mikrochirurgischer skleraeindellender Ablatiochirurgie.

BACKGROUND: The purpose of this study is to report the long-term results of a refined scleral buckling technique for the treatment of retinal detachments. PATIENTS/MATERIALS AND METHODS: We retrospectively reviewed the charts of 152 consecutive cases (129 patients), operated in our clinic by one surgeon. Indirect ophthalmoscopy was used for the identification and treatment of retinal breaks. All other steps of the operation were performed under the operating microscope. The main outcome measures were the retinal redetachment rate, intraoperative and postoperative complication rates as well as the functional outcome. RESULTS: Reattachment was achieved in 130 eyes (85.5 %) after the first procedure and in 151 eyes (99.3 %) after reoperation. No intraoperative complications occurred in our series. Eighty-one eyes (53.3 %) showed a significant improvement in visual acuity after surgery, whereas 16 eyes (10.5 %) showed a significant deterioration in visual acuity. At the last follow-up visit, 101 cases (66.4 %) showed a visual acuity of 0.5 or better, 68 cases (44.7 %) had a visual acuity of 0.8 or better and in 7 cases (4.6 %) the visual acuity was lower than 0.1. CONCLUSIONS: Adding microsurgical techniques to scleral buckle surgery may help to minimise the incidence of intraoperative and postoperative complications resulting in a favourable functional outcome.

Transcript lifetime is balanced between stabilizing stem-loop structures and degradation-promoting polyadenylation in plant mitochondria.

To determine the influence of posttranscriptional modifications on 3' end processing and RNA stability in plant mitochondria, pea atp9 and Oenothera atp1 transcripts were investigated for the presence and function of 3' nonencoded nucleotides. A 3' rapid amplification of cDNA ends approach initiated at oligo(dT)-adapter primers finds the expected poly(A) tails predominantly attached within the second stem or downstream of the double stem-loop structures at sites of previously mapped 3' ends. Functional studies in a pea mitochondrial in vitro processing system reveal a rapid removal of the poly(A) tails up to termini at the stem-loop structure but little if any influence on further degradation of the RNA. In contrast 3' poly(A) tracts at RNAs without such stem-loop structures significantly promote total degradation in vitro. To determine the in vivo identity of 3' nonencoded nucleotides more accurately, pea atp9 transcripts were analyzed by a direct anchor primer ligation-reverse transcriptase PCR approach. This analysis identified maximally 3-nucleotide-long nonencoded extensions most frequently of adenosines combined with cytidines. Processing assays with substrates containing homopolymer stretches of different lengths showed that 10 or more adenosines accelerate RNA processivity, while 3 adenosines have no impact on RNA life span. Thus polyadenylation can generally stimulate the decay of RNAs, but processivity of degradation is almost annihilated by the stabilizing effect of the stem-loop structures. These antagonistic actions thus result in the efficient formation of 3' processed and stable transcripts.

Derivation of sonograph quality parameters by the use of point spread function analysis.

A measuring system evaluating a Point Spread Function generated in an ultrasonographic image by scanning a spherical target was developed. The target is moved in measuring bath filled by water over scanned volume via 3D computer controlled positioning system. A video signal obtained is converted to digital form and analyzed by original software to derive various objective parameters of the imager as follows: Focal areas in both the azimuth and the elevation directions, Ultrasound scanning lines visualisation, Manufacturer preloaded TGC, Width of the scanning plane, Side lobe levels and Amplification uniformity in the azimuth direction. The method was verified by testing 18 different equipments in 282 measurements. Samples of particular measurement results in form of graphical outputs are included. Medical and physiological impacts of this approach are discussed.

Long term results after transpupillary thermotherapy in eyes with occult choroidal neovascularisation associated with age related macular degeneration: a prospective trial.

AIM: To evaluate long term results after transpupillary thermotherapy (TTT) in eyes with exudative age related macular degeneration. METHODS: In a prospective clinical study eyes with occult or predominantly occult choroidal neovascularisation and no pretreatment were scheduled to have a TTT with a power of 630 mW. Visual acuity for far and near distances as well as contrast sensitivity were evaluated 6, 12, and 24 months postoperatively and statistically analysed. RESULTS: 47 eyes fulfilled the inclusion criteria. Overall, 70% of the patients showed an improved (14%) or had unchanged (56%) ETDRS vision after 24 months. Reading vision was stabilised (51%) or better (5%) in 56% of the eyes at this time. However, the increasing number of eyes with severe deterioration resulted in a significant decrease of both parameters over time (p = 0.0002 and p = 0.0003, respectively). Contrast sensitivity could be maintained (70%) or improved (9%) in 79%. Statistical analyses indicated a trend but no significant decrease over time (p = 0.056). CONCLUSION: Although in the majority of patients far and near distance acuity could be stabilised on average a significant decrease over time after TTT was observed. Statistical comparison of months 12 and 24 showed no further deterioration.

The RNA world of plant mitochondria.

Mitochondria are well known as the cellular power factory. Much less is known about these organelles as a genetic system. This is particularly true for mitochondria of plants, which subsist with respect to attention by the scientific community in the shadow of the chloroplasts. Nevertheless the mitochondrial genetic system is essential for the function of mitochondria and thus for the survival of the plant. In plant mitochondria the pathway from the genetic information encoded in the DNA to the functional protein leads through a very diverse RNA world. How the RNA is generated and what kinds of regulation and control mechanisms are operative in transcription are current topics in research. Furthermore, the modes of posttranscriptional alterations and their consequences for RNA stability and thus for gene expression in plant mitochondria are currently objects of intensive investigations. In this article current results obtained in the examination of plant mitochondrial transcription, RNA processing, and RNA stability are illustrated. Recent developments in the characterization of promoter structure and the respective transcription apparatus as well as new aspects of RNA processing steps including mRNA 3' processing and stability, mRNA polyadenylation, RNA editing, and tRNA maturation are presented. We also consider new suggestions concerning the endosymbiont hypothesis and evolution of mitochondria. These novel considerations may yield important clues for the further analysis of the plant mitochondrial genetic system. Conversely, an increasing knowledge about the mechanisms and components of the organellar genetic system might reveal new aspects of the evolutionary history of mitochondria.

Variables and specificity of in vitro lymphocyte-mediated cytotoxicity in human melanoma.

In vitro cell-mediated cytotoxicity (CMC) assays have been carried out in human melanoma system with blood effector lymphocytes on [3H]proline-labeled target cells in a 48-hr microcytotoxicity technique. Three lymphocyte purification procedures (Ficoll:Hypaque gradient, plasma gel sedimentation followed by nylon column incubation, and plasma gel sedimentation followed by separation with nylon powder and glass beads) are compared in parallel experiments for characteristic effector cell composition and cytotoxic potential against target cells of dissimilar histology. The cytotoxicity is defined by the loss of target cell 3H cpm as measured by residual target cell 3H cpm in individual microwell following incubation with lymphocytes. Target cell 3H cpm loss by test lymphocytes is compared with target cell 3H cpm loss by several age and sex matched control lymphocytes (from normal donors and unrelated cancer patients); further comparison between the various control lymphocytes is also made in each assay. As control for target cells, autologous fibroblasts and homologous tumor cells of dissimilar histology are always included in each assay. Specific cytotoxicity is defined as statistically significant and selective destruction of only melanoma cells by the test lymphocytes as compared to the control lymphocytes. Significant but nonselective destruction of 2 or more target cells of unrelated histology is regarded as nonspecific cytotoxicity, while no destruction of any target cells signifies no cytotoxicity. The Ficoll:Hypaque preparations consistently exhibit the highest nonlymphocytic cell contamination (8 to 16%); the nonlymphocytic cells are, almost exclusively, monocytes. They also produce relatively high percentage of thymus independent (B) cells (8 to 15%). The ultimate cell composition of the 2 plasma gel-nylon preparations is essentially identical. In either plasma gel-nylon preparations, the nonlymphocytic contamination is minimal (0 to 4%) and thymus-dependent (T) cell percentage is considerably higher (92 to 99%) with none or few B cells.

RNA editing.

The term RNA editing describes those molecular processes in which the information content is altered in an RNA molecule. To date such changes have been observed in tRNA. rRNA and mRNA molecules of eukaryotes, but not prokaryotes. The demonstration of RNA editing in prokaryotes may only be a matter of time, considering the range of species in which the various RNA editing processes have been found. RNA editing occurs in the nucleus, as well as in mitochondria and plastids, which are thought to have evolved from prokaryotic-like endosymbionts. Most of the RNA editing processes, however, appear to be evolutionarily recent acquisitions that arose independently. The diversity of RNA editing mechanisms includes nucleoside modifications such as C to U and A to I deaminations, as well as non-templated nucleotide additions and insertions. RNA editing in mRNAs effectively alters the amino acid sequence of the encoded protein so that it differs from that predicted by the genomic DNA sequence.

Intravitreal anti-vascular endothelial growth factor combined with half-fluence photodynamic therapy for choroidal neovascularization in chronic central serous chorioretinopathy.

PurposeTo evaluate the results of indocyanine green angiography (ICGA)-guided verteporfin photodynamic therapy (PDT) with half-fluence rate combined with intravitreal application of anti-VEGF in treating choroidal neovascularization (CNV) in chronic central serous chorioretinopathy (CSCR).Patients and methodsIn this retrospective cohort study 17 consecutive patients with secondary CNV due to chronic CSCR had their diagnosis verified with fluorescein angiography (FA) and ICGA at baseline. All eyes received either intravitreal ranibizumab (IVR) or bevacizumab (IVB). On the consecutive day following the initial IVR/IVB treatment, ICGA-guided verteporfin (6 mg/m(2)) PDT with half-fluence rate (25 J/cm(2)) was performed on every patient. IVR or IVB was rescheduled on a pro re nata regimen. Main outcome measures were changes in visual acuity (VA) according to the ETDRS letter score and changes in the central foveal thickness (CFT).ResultsBest-corrected VA at baseline was 65.6 letters (±6.7; n=17) according to the ETDRS letter score. At 12 months, mean ETDRS letter score improved to 71.2 letters (P=0.34). CFT was 309 µm and decreased to 216 µm at month 12 control (P=0.0004). Nine eyes (52.9%) received additional treatment with IVR/IVB due to recurrence of subretinal fluid, with an overall mean number of IVR/IVB treatment of 1.8±3.6 per patient with no systemic side effects during 12 months' follow-up.ConclusionsIVR or IVB combined with ICGA-guided half-fluence PDT with verteporfin is effective in treating CNV in chronic CSCR, with choroidal hyperpermeability in ICGA, resulting in stable vision and significant reduction of CFT.

Deubiquitylating enzyme USP9x regulates radiosensitivity in glioblastoma cells by Mcl-1-dependent and -independent mechanisms.

Glioblastoma is a very aggressive form of brain tumor with limited therapeutic options. Usually, glioblastoma is treated with ionizing radiation (IR) and chemotherapy after surgical removal. However, radiotherapy is frequently unsuccessful, among others owing to resistance mechanisms the tumor cells have developed. Antiapoptotic B-cell leukemia (Bcl)-2 family members can contribute to radioresistance by interfering with apoptosis induction in response to IR. Bcl-2 and the closely related Bcl-xL and Mcl-1 are often overexpressed in glioblastoma cells. In contrast to Bcl-2 and Bcl-xL, Mcl-1 is a short-lived protein whose stability is closely regulated by ubiquitylation-dependent proteasomal degradation. Although ubiquitin ligases facilitate degradation, the deubiquitylating enzyme ubiquitin-specific protease 9x (USP9x) interferes with degradation by removing polyubiquitin chains from Mcl-1, thereby stabilizing this protein. Thus, an inability to downregulate Mcl-1 by enhanced USP9x activity might contribute to radioresistance. Here we analyzed the impact of USP9x on Mcl-1 levels and radiosensitivity in glioblastoma cells. Correlating Mcl-1 and USP9x expressions were significantly higher in human glioblastoma than in astrocytoma. Downregulation of Mcl-1 correlated with apoptosis induction in established glioblastoma cell lines. Although Mcl-1 knockdown by siRNA increased apoptosis induction after irradiation in all glioblastoma cell lines, USP9x knockdown significantly improved radiation-induced apoptosis in one of four cell lines and slightly increased apoptosis in another cell line. In the latter two cell lines, USP9x knockdown also increased radiation-induced clonogenic death. The massive downregulation of Mcl-1 and apoptosis induction in A172 cells transfected with USP9x siRNA shows that the deubiquitinase regulates cell survival by regulating Mcl-1 levels. In contrast, USP9x regulated radiosensitivity in Ln229 cells without affecting Mcl-1 levels. We conclude that USP9x can control survival and radiosensitivity in glioblastoma cells by Mcl-1-dependent and Mcl-1-independent mechanisms.

Characterization of DNA-Binding Proteins from Pea Mitochondria

We studied transcription initiation in the mitochondria of higher plants, with particular respect to promoter structures. Conserved elements of these promoters have been successfully identified by in vitro transcription systems in different species, whereas the involved protein components are still unknown. Proteins binding to double-stranded oligonucleotides representing different parts of the pea (Pisum sativum) mitochondrial atp9 were analyzed by denaturation-renaturation chromatography and mobility-shift experiments. Two DNA-protein complexes were detected, which appeared to be sequence specific in competition experiments. Purification by hydroxyapatite, phosphocellulose, and reversed-phase high-pressure liquid chromatography separated two polypeptides with apparent molecular masses of 32 and 44 kD. Both proteins bound to conserved structures of the pea atp9 and the heterologous Oenothera berteriana atp1 promoters and to sequences just upstream. Possible functions of these proteins in mitochondrial promoter recognition are discussed.

Evaluation of the BioPlex 2200 ANA screen: analysis of 510 healthy subjects: incidence of natural/predictive autoantibodies.

The BioPlex 2200 ANA Screen is a fully automated system that determines levels for 13 different autoimmune antibodies of established clinical significance. The objective of this study was to determine the specificity of the BioPlex 2200 ANA Screen assay and to analyze the antibody profile samples collected from healthy subjects against comparative ELISA and IIF screening methods. A total of 510 specimens were randomly selected from a cohort of apparently healthy blood bank donors. Samples were distributed to five age brackets. All samples were tested using Bio-Rad's ANA Screen kit. Specificity was compared to IIF and ELISA results. Most of the samples were found negative in all ANA screening systems (84.5% by IIF, 92.5% by BioPlex 2200 ANA Screen kit, and 94.5% by ELISA). The frequency of positive results was highest (15.5%) using IIF, in comparison to almost similar results (5.5% vs. 7.5%) achieved by ANA ELISA and BioPlex 2200 ANA Screen kits. The positive rate of autoantibodies was significantly reduced when analyzed by different combinations of ANA screen assays (from 2.35% using IIF + BioPlex ANA Screen tests to 0.98% by using all three tests). Using the BioPlex 2200 ANA Screen system, we were able to identify samples with high levels of individual antibodies: anti-dsDNA at 20-63 IU/mL, antichromatin at 4-8 AI, anti-SmRNP at 2-6 AI, and anti-RNPA at 2-4.5 AI. Importantly, from 7 IIF and ELISA positive sera, 5 of these were also BioPlex 2200 positive, suggesting that the BioPlex is seeing the samples that are of the greatest interest, using the established techniques. The specificity of the BioPlex 2200 ANA Screen analysis of 13 different analytes (dsDNA, centromere B, chromatin, Jo1, ribosomal P, RNP 68, RNP A, Scl-70, Sm, SmPNP, SS-A52, SS-A60, SS-B) is comparable (P < 0.252) to the ELISA ANA screening test. Like the ELISA, the BioPlex 2200 has a lower (P < 0.001) positive rate than IIF for the autoantibody screening.